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• Mechanisms that establish polarity and pattern in vertebrates
• Maternally deposited factors in early development and the mechanisms of localization of maternal determinants.
• Developing methods to identify localized molecules in zebrafish

Research Projects

The Vertebrate Development group is interested in understanding the mechanisms by which polarity and pattern are established in vertebrate embryos, using zebrafish as a model organism.  We have been studying some of these processes using mutations in the TGF-beta related Nodal signaling pathway.  Mutations in the zebrafish nodal gene, cyclops, results in deficiencies of the ventral neural tube, reduced prechordal plate mesendoderm, and cyclopia. We isolated a temperature-sensitive mutation affecting the cyclops locus, and used it to show that the floor plate of the neural tube is induced during gastrulation, and that continuous Cyclops signaling is essential for a complete ventral neural tube in zebrafish (Tian et al., 2003). In addition to its role during embryogenesis, we find that transcripts of cyclops and the related squint gene are expressed maternally, and are asymmetrically localized in oocytes in the ovary and embryo (Gore and Sampath 2002, Gore et al., 2005; and our unpublished data), suggesting additional functions for these molecules in polarity and patterning. We find that asymmetrically localized squint RNA can predict the future dorsal side of the embryo as early as cleavage stages. Our current efforts are aimed at identifying the factors that localize squint RNA in the early embryo. Some related issues that we are addressing include:

• Identification of localized molecules in the egg and embryo. Towards this end, we are developing a gene trap system to identify maternally localized factors. A pilot screen testing various gene traps is in progress.
• Determining the functions of maternal factors in establishing oocyte and embryonic polarity
• Determining the mechanisms by which squint and cyclops RNA are localized.
• Understanding the molecular basis for the differences in activities between Cyclops and Squint in the egg and embryo
• Understanding the mechanisms by which Cyclops induces specific fates in the embryo